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The surprising features of the TEAD4-Vgll1 protein-protein interaction

Mesrouze, Yannick and Hau, Jean-Christophe and Erdmann, Dirk and Zimmermann, Catherine and Fontana, Patrizia and Schmelzle, Tobias and Chene, Patrick (2014) The surprising features of the TEAD4-Vgll1 protein-protein interaction. ChemBioChem, 15 (4). pp. 537-542. ISSN 1439-4227

Abstract

The Hippo signaling pathway, which controls organ size in animals, is altered in various human cancers. The TEAD transcription factors, the most downstream elements in this pathway, are regulated by different cofactors, such as the Vgll (vestigial-like) proteins. Having studied the interaction between Vgll1-derived peptides and human TEAD4, we show that, although it lacks a key secondary structure element required for tight binding by two other TEAD cofactors (YAP and TAZ), Vgll1-derived peptides bind to TEAD with nanomolar affinity. We identify a β-strand:loop:α-helix motif as the minimal Vgll binding site. Finally, we reveal an unexpected difference between mouse and human Vgll1-derived peptides. Shared interests: TEAD transcription factors are regulated by cofactors such as Vgll, YAP, and TAZ. Vgll1 (blue) binds to TEAD at a similar site to YAP/TAZ (red) but lacks the Ω-loop that confers high affinity. Synthetic peptides mimicking Vgll1 also bind to TEAD with nanomolar affinity, and we reveal an unexpected difference between mouse and human Vgll1-derived peptides. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Item Type: Article
Additional Information: Unmapped bibliographic data: LA - English [Field not mapped to EPrints] ST - The surprising features of the TEAD4-Vgll1 protein-protein interaction [Field not mapped to EPrints] AU - Mesrouze, Y. [Field not mapped to EPrints] AU - Hau, J. C. [Field not mapped to EPrints] AU - Erdmann, D. [Field not mapped to EPrints] AU - Zimmermann, C. [Field not mapped to EPrints] AU - Fontana, P. [Field not mapped to EPrints] AU - Schmelzle, T. [Field not mapped to EPrints] AU - Chene, P. [Field not mapped to EPrints] AD - (Mesrouze, Hau, Erdmann, Zimmermann, Fontana, Schmelzle, Chene) Disease Area Oncology, Novartis Institutes for Biomedical Research, 141 Klybeckstrasse, 4057 Basel, Switzerland [Field not mapped to EPrints] DB - Embase [Field not mapped to EPrints] DP - Ovid Technologies [Field not mapped to EPrints] AN - 2014158080 [Field not mapped to EPrints]
Keywords: Hippo pathway peptides protein-protein interactions TAZ TEAD Vgll proteins YAP
Date Deposited: 28 Nov 2017 00:45
Last Modified: 25 Jan 2019 00:46
URI: https://oak.novartis.com/id/eprint/20276

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